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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EMajor depressive disorder (MDD) affects about 15 million adults in the United States. Within that population, only one-third of patients who are treated with first-line antidepressant therapies achieve remission [Trivedi MH, Papakostas G, Perlis R. APA 2009]. Therefore, therapeutic augmentation, the addition of nonantidepressant compounds to an antidepressant regimen, may be a more reasonable option for those patients with first-line treatment resistance. This article explores the issue of treatment resistance in MDD and possible management strategies.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPsychopharmacology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMood Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMajor depressive disorder (MDD) affects about 15 million adults in the United States. Within that population, only one-third of patients who are treated with first-line antidepressant therapies achieve remission [Trivedi MH, Papakostas G, Perlis R. APA 2009]. Therefore, therapeutic augmentation, the addition of nonantidepressant compounds to an antidepressant regimen, may be a more reasonable option for those patients with first-line treatment resistance. Several experts in the field explored the issue of treatment resistance in MDD and possible management strategies at the American Psychiatric Association annual meeting.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ERoy Perlis, MD, MSc, Massachusetts General Hospital, Boston, MA, discussed possible predictors and second-line approaches for MDD patients with differential responses to antidepressant monotherapy. He pointed out that there are 2 kinds of predictors that are related to inadequate response: nonspecific predictors that are related to poor overall response (ie, greater depression severity, socioeconomic status, gender, and level of anxiety or irritability) and drug-specific predictors (ie, decreased SSRI response but adequate SNRI response) [Cohen A et al. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 2006; Trivedi MH et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006; Fava M et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2008]. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, higher levels of anxiety and irritability in MDD patients who were treated with either monotherapy or an augmented antidepressant regimen were associated with poorer treatment outcomes (p\u0026lt;0.05) [Fava M et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2008]. Based on these results, Prof. Perlis said, \u201cPeople with higher levels of irritability or anxiety during depression probably merit particular attention, because their likelihood of remitting is lower than those without these symptoms.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ETreatment-emergent suicidal ideation also remains a problem in the management of MDD. Prof. Perlis discussed possible biomarkers that are related to this issue. In a study by Laje and colleagues, 2 biomarkers within GRIK2 and GRIA3 (rs4825476 and rs2518224) were associated with treatment-emergent suicidal ideation during citalopram therapy (rs4825476 permutation p=0.01; rs2518224 permutation p=0.003) [Laje G et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2007]. In a study by Perlis and colleagues, polymorphisms that span cyclic adenosine monophosphate response element-binding (CREB1) protein were associated with treatment-emergent suicidality among men with depression [Perlis RH et al. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 2007]. However, these studies have not yet been replicated, so further investigation is warranted.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThere are some possible biomarkers that may predict treatment resistance and poor response. There are commercially available tests for poor metabolizers that involve cytochrome p450 variation, particularly in patients with multiple instances of intolerance at low doses or nonresponse despite aggressive dosing. Prof. Perlis emphasized that there is no evidence that these tests are useful for choosing antidepressants; they are more expensive than standard blood level testing; and they only test 1 factor and do not take into account other variables, such as diet, adherence, and other comorbidities. Therefore, blood levels are more clinically useful.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EGenomewide association studies have also investigated antidepressant efficacy in MDD, but no single gene has consistently appeared at the top of the list for antidepressant response across studies. \u201cMost likely when we get there, it will be with a combination of many genes rather than a single gene,\u201d said Prof. Perlis.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EMudhukar Trivedi, MD, University of Texas, Southwestern Medical Center, Dallas, TX, discussed various augmentation strategies prior to and in conjunction with the STAR*D trial. Lithium augmentation has the most evidence with regard to overall response (p=0.0001) and rapid response rate, although most of the published studies are small [Crossley NA \u0026amp; Bauer M. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2007; Thase ME, Rush AJ. Psychopharmacology: The Fourth Generation of Progress, 1995]. Augmentation with triiodothyronine (T\u003Csub\u003E3\u003C\/sub\u003E) has also had promising results. A meta-analysis of 8 T\u003Csub\u003E3\u003C\/sub\u003E augmentation trials by Aronson and colleagues demonstrated that patients who were treated with T\u003Csub\u003E3\u003C\/sub\u003E augmentation were twice as likely to respond as controls (OR, 2.09; 95% CI, 1.31 to 3.32; p=0.002) [Aronson R. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 1996]. Additionally, augmentation with buspirone has demonstrated safety and efficacy [Spier S. \u003Cem\u003EDepress Anxiety\u003C\/em\u003E 1998; Lam R et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2004]. However, the published T\u003Csub\u003E3\u003C\/sub\u003E and buspirone studies were small, and results were inconsistent.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe STAR*D study was a large trial that consisted of 4 levels of treatment, beginning with citalopram only and moving to alternative treatment or augmentation depending on patient response (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The STAR*D remission rates (based on HAM-D-17\u0026lt;8) for all levels of the study were slightly better for patients who were undergoing augmentation versus monotherapy [McGrath PJ et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006; Rush AJ et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006; Nierenberg AA et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006; Trivedi MH et al. \u003Cem\u003EJ Clin Psychiatr.\u003C\/em\u003E 2006; Trivedi MH et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006]. A one-third remission rate was noted in patients who were undergoing augmentation therapy in levels 2 and 3 of the study (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E). Prof Trivedi said that although the rates of remission were modest in STAR*D, the study demonstrated the need for a multitiered approach, more aggressive treatment options, and measurement-based care.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022STAR*D Treatment Algorithm Snapshot.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1066366902\u0022 data-figure-caption=\u0022STAR*D Treatment Algorithm Snapshot.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11322\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003ESTAR*D Treatment Algorithm Snapshot.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022STAR*D Clinical Study Results.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1066366902\u0022 data-figure-caption=\u0022STAR*D Clinical Study Results.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11325\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ESTAR*D Clinical Study Results.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EOther potential augmentation strategies include mirtazapine, psychostimulants, folic acid, and estrogen therapies. A folic acid augmentation study by Coppen and Bailey demonstrated improvement in Hamilton Rating Scales in the fluoxetine plus folic acid group versus placebo. This was confined to women, in whom the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4.1) in the fluoxetine plus folate group, as compared with 11.7 (S.D. 6.7) in the fluoxetine plus placebo group (p\u0026lt;0.001) [Coppen A, Bailey J. \u003Cem\u003EJ Affect Disord\u003C\/em\u003E 2000]. There was no significant change in men. The folic acid and other augmentation treatments have been investigated in very small studies to date, and although the preliminary data have been promising with regard to safety and efficacy, larger randomized, controlled trials are needed to establish their feasibility as augmentation alternatives for MDD.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EProf. Trivedi also noted that residual symptoms, such as insomnia and fatigue, are problems for those who do not attain remission, and it is important to select agents that may match\/treat residual symptoms. Residual symptoms are associated with an increased risk for relapse and increased psychosocial impairments.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EGeorge Papakostas, MD, Massachusetts General Hospital, Boston, MA, discussed the use of atypical antipsychotics in the management of MDD. Risperidone, quetiapine, olanzapine, and aripiprazole have been investigated as possible augmentation agents for patients with MDD, but it is important to balance the risks and benefits of these treatment strategies [Papkostas GI et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2007]. Thirty-seven percent of patients within these trials discontinued the augmentation component of therapy due to intolerance (p\u0026lt;0.05) [Papkostas GI et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2007]. Weight gain was significantly higher among patients who received either risperidone (a difference of 2.5 to 4.0 lbs in 4 weeks vs placebo) or aripiprazole (mean change from baseline at 6 weeks, 3.7 lbs) versus placebo [Keitner GI et al. \u003Cem\u003EJ Psychiatric Res\u003C\/em\u003E 2009; Berman R et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2007; Marcus R et al. \u003Cem\u003EJ Clin Psychopharmacol\u003C\/em\u003E 2008]. Significant changes in metabolic and endocrine parameters were noted with quetiapine and olanzapine (p\u0026lt;0.05 for both; \u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigures 3\u003C\/a\u003E and \u003Ca id=\u0022xref-fig-4-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F4\u0022\u003E4\u003C\/a\u003E) augmentation [Thase ME at al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2007; Bauer M et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2009]. Other tolerability issues that were associated with aripiprazole augmentation included akathisia, restlessness, insomnia, fatigue, blurred vision, and constipation. Somnolence, hypersomnia, edema, and dry mouth were associated with olanzapine augmentation.\u003C\/p\u003E\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Olanzapine Augmentation in TRD: Changes in Metabolic and Endocrine Patterns.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1066366902\u0022 data-figure-caption=\u0022Olanzapine Augmentation in TRD: Changes in Metabolic and Endocrine Patterns.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11328\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n            \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003EOlanzapine Augmentation in TRD: Changes in Metabolic and Endocrine Patterns.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022F4\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F4.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Quetiapine Augmentation in TRD: Changes in Metabolic and Endocrine Patterns.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1066366902\u0022 data-figure-caption=\u0022Quetiapine Augmentation in TRD: Changes in Metabolic and Endocrine Patterns.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 4.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F4.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F4.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 4.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F4.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11331\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 4.\u003C\/span\u003E \n            \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003EQuetiapine Augmentation in TRD: Changes in Metabolic and Endocrine Patterns.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003EProf. Papakostas also presented the evidence-based benefits of augmentation therapy that were related to atypical antipsychotics. In a study by Shelton and colleagues, 28 treatment-resistant MDD patients were randomized to receive either fluoxetine (mean 52 mg daily) plus placebo, olanzapine (mean 12.5 mg daily) plus placebo, or olanzapine plus fluoxetine (mean 13.5 mg\/52 mg daily). Although this was a small study, patients in the olanzapine plus fluoxetine arm showed rapid clinical improvement, and olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared with either agent alone (p\u0026lt;0.05) [Shelton RC et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2001]. Three larger studies compared aripiprazole augmentation with placebo, resulting in a 26% to 36.8% remission rate for the aripiprazole augmentation groups (p\u0026lt;0.05) [Berman R, et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2007; Marcus R et al. \u003Cem\u003EJ Clin Psychopharmacol\u003C\/em\u003E 2008; Berman R et al. \u003Cem\u003ECNS Spectrums\u003C\/em\u003E 2009]. Results of 2 randomized, double-blind, placebo-controlled trials that compared quetiapine (150 mg\/day and 300 mg\/day) augmentation versus placebo demonstrated significant MADRS score reduction in the quetiapine groups (p\u0026lt;0.05; \u003Ca id=\u0022xref-fig-5-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F5\u0022\u003EFigure 5\u003C\/a\u003E) [Bauer M et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2009; El-Khalili N et al. \u003Cem\u003E161st Annual APA Meeting;\u003C\/em\u003E May 2008].\u003C\/p\u003E\u003Cdiv id=\u0022F5\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F5.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Quetiapine Augmentation: Results of Two Randomized, Double-Blind, Placebo-Controlled Trials.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1066366902\u0022 data-figure-caption=\u0022Quetiapine Augmentation: Results of Two Randomized, Double-Blind, Placebo-Controlled Trials.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 5.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F5.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F5.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 5.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/24\/F5.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11332\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 5.\u003C\/span\u003E \n            \u003Cp id=\u0022p-17\u0022 class=\u0022first-child\u0022\u003EQuetiapine Augmentation: Results of Two Randomized, Double-Blind, Placebo-Controlled Trials.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-18\u0022\u003EAripiprazole and olanzapine are the first agents to receive an indication from the Food and Drug Administration as adjunctive therapy for treatment-resistant MDD, although further research that investigates long-term efficacy, safety, and tolerability is needed with regard to the use of atypical antipsychotics as augmentation therapy. \u201cClearly, even though this appears to be a promising strategy,\u201d said Prof. Papkostas, \u201cI think we have a ways to go in terms of further delineating the clinical niche and the clinical properties of this treatment strategy.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003ETherapeutic augmentation for treatment-resistant MDD is a complex approach that is still in its clinical infancy. There are many exciting new options and potential tools that may assist physicians in further enhancing outcomes through individualized treatment, but this issue merits further investigation before a specific clinical regimen can be established.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2009 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/9\/3\/24.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmk01\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmk01\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}